Cancer Control Group Research Articles

Evaluation of tumor-suppressive properties and apoptotic functions of Mad Honey and Vincristine applications in a rat model of breast cancer

In this study, the suppressive effects of vincristine and Turkish mad honey alone and in co-applications were biochemically, hematologically, and histopathologically investigated in a mammary tumor model induced with 7,12-dimethylbenz[a]anthracene (DMBA) in rats. A total of 72 rats, 43-49 days old, were divided into 6 groups of 12 rats each. The control group (CG) consisted of healthy rats. The vehicle group (VG) received only vehicle substance and the cancer control group (CCG) was given only DMBA. DMBA and the honey group (HG) given group. DMBA and the vincristine (VinG) given group, and DMBA, the vincristine-honey group (VHG) received both Turkish mad honey and vincristine. Turkish mad honey and/or vincristine was given in the last 4 weeks of the 13-week trial period. White blood cell and lymphocyte counts differed significantly in the CCG and VG groups. Alanine transaminase and total protein levels were higher in the CCG and VinG groups. Aspartate transaminase was higher in the CCG, HG and VG groups. Caspase-3 and Bax protein levels were in the HG and VHG groups significantly higher than CCG. In caspase-8 protein level VHG significantly higher than other groups. Caspase -9 protein level was in CG and VG groups significantly lower than other groups. Bcl-xL increased more in the CCG group. Anaplasia was reduced in the HG and VinG groups, although apoptosis and other cellular damages increased. It was concluded that mad honey and vincristine could be considered together as effective therapeutic agents in this model of DMBA-induced breast cancer.

<i>Tarantula cubensisalcohol</i> extract enhances the tumoricidal effect of capecitabine via multiple pathways in azoxymethane-induced colorectal cancer in rats

Purpose: To evaluate the effect of a combination of Tarantula cubensis alcohol extract (TCAE) and capecitabine (CAP) in the treatment of azoxymethane (AOM)-induced colorectal cancer (CRC). 
 Methods: Forty-two Wistar albino rats were divided into 7 groups with 6 rats in each group. The groups consisted of Control (C), Control+TCAE (C-TCAE), Control+CAP (C-CAP), Cancer control (CC), Cancer+TCAE (CC-TCAE), Cancer+CAP (CC-CAP) and Cancer+CAP+TCAE (CC-CAP+TCAE). To induce CRC, AOM (15 mg/kg) was administered to rats subcutaneously (sc) twice at a one-week interval to all the groups except control. From the 15th week, TCAE (0.2 mL/rat sc) was administered to CC-TCAE group every 3 days for 4 weeks, and CAP (40 mg/kg/day) was administered by gavage to CC-CAP group for 4 weeks. In CC-CAP+TCAE group, TCAE (0.2 mL/rat sc) was administered every 3 days for 4 weeks, and CAP (40 mg/kg/day) was administered gavage for 4 weeks. Animals were treated for 18 weeks. Aberrant crypt foci (ACF) were evaluated histopathologically among CC, CC-TCAE, CC-CAP, and CC-CAP+TCAE groups. β-catenin, CD15, Proliferating Cell Nuclear Antigen (PCNA), and Nuclear Factor kappa B (NF-κB) expression levels were immunohistochemically compared among all groups. 
 Results: Histopathologically, ACF scores were significantly increased in CC group, while a significant decrease in the relevant scores (p < 0.001) was observed in CC-CAP and CC-CAP+TCAE treatment groups, and the lowest scores were in CC-CAP+TCAE group. Immunohistochemically, in CC group, β-catenin, Nuclear Factor kappa B (NF-κB), Proliferating Cell Nuclear Antigen (PCNA) and CD15 expressions were highly irregular. CC-CAP and CC-CAP+TCAE groups had significantly reduced expressions (p < 0.001), and the lowest expressions were in CC-CAP+TCAE group. 
 Conclusion: The combined use of TCAE and CAP in treatment of CRC has a synergistic effect and increases the anticancer efficacy of TCAE, and CAP. More studies at the molecular level are needed in the future to demonstrate the clinical benefit of TCAE supplementation during the treatment of CRC with CAP.

Evaluation of the combined effects of Turkish mad honey and 5-Fluorouracil in colon cancer model in rats

It was aimed to evaluate the regressive effect of grayanotoxin-rich Turkish mad honey and 5-fluorouracil (5-FU), separately and together by using the N-methyl-N-nitrosourea (MNU)-induced colon cancer modelling in rats. Study groups were designed as control group (CG), cancer control group (CCG), 5-Flourouracil group (FUG), Turkish mad honey group (HG), Turkish mad honey and 5-FU combined group (FU-HG). White blood cell (WBC), lymphocyte, eosinophil, basophil, serum lactate dehydrogenase (LDH), total oxidant status (TOS), and total protein values of the rats in the CCG were significantly lower than the values of the rats in the CG, whereas serum Bcl-2 and survivin levels were significantly higher in the rates belonged to the CCG in comparison to those in the CG. The presence of anaplastic epithelial cells, vascularization, precancerous changes, and inflammatory infiltration detected in the colon and small intestine of the rats in FU-HG, FUG, HG were less intense (P<0.05) compared to the findings in the rats in CCG. In conclusion, mad honey and 5-FU reduced anaplastic cell growth and oxidative stress via suppressed anti-apoptotic activity. Considering the histopathological findings in the liver and kidney, no toxicity occurred related to mad honey and 5-FU metabolization. Therefore, the combined use of these two substances may be an alternative method in the treatment of colon cancer.

Effect of Tarantula cubensis alcoholic extract on tumour pathways in azoxymethane-induced colorectal cancer in rats

The aim of this study was to determine the effects of Tarantula cubensis alcoholic extract (TCAE) on tumour development pathways in azoxymethane (AOM)-induced colorectal cancer in rats by molecular methods. Eighteen paraffin-embedded intestinal tissues, six from each group, were studied in the healthy control (C), cancer control (CC), cancer + TCAE (C-TCAE) groups. Sections of 5 µm thickness were taken from the paraffin blocks and submitted to staining with haematoxylin-eosin. In the histopathological examination, the number of crypts forming aberrant crypt foci (ACF) and the degree of dysplasia in the crypts were scored. Real-time PCR analysis was completed to determine β-catenin, KRAS (Kirsten rat sarcoma virus), APC (adenomatous polyposis coli) and P53 expressions on samples from each paraffin block. The grading scores of the number of crypts forming ACF and dysplasia in the crypts showed an evident decrease in the C-TCAE group in comparison to the CC group (P < 0.05). In real-time PCR analysis, mRNA expression levels of P53 (P > 0.05) and APC (P < 0.001) genes were found to be increased in the C-TCAE group according to the CC group. The expression levels of KRAS (P < 0.01) and β-catenin (P < 0.005) mRNA were found significantly decreased in the C-TCAE group. In conclusion, the effects of TCAE on AOM-induced colorectal cancer (CRC) in rats were evaluated molecularly; TCAE was found to modulate some changes in CRC developmental pathways, inhibiting tumour development and proliferation, and stimulating non-mutagenic tumour suppressor genes. Thus, it can be stated that TCAE is an effective chemopreventive agent.

Aerobic Training and Green Tea Extract Protect against N-methyl-N-nitrosourea-induced Prostate Cancer.

Aerobic training and green tea extract can be used to reduce the risk of prostate cancer. The goal of this study was to evaluate the effects of 8-wk aerobic exercise training and administration of green tea extract on the level of nuclear factor kappa B (NF-kB), cyclooxygenase-2 (COX-2) and p53 tumor suppressor protein (p53) in prostate of rats which were stimulated by N-methyl-N-nitrosourea to induce the prostate cancer. Sixty adult male Wistar rats were assigned into six groups including healthy control, cancer control (CCt), cancer training (CTr: 45 min·d at low to moderate intensity, five times per week, 8 wk), cancer extract (CEx: 1.34 mL of green tea extract, three times per week, 8 wk), cancer training+ cancer extract (CTr + CEx) and sham groups. Rats were sacrificed 48 h after the last intervention session, and the prostate tissue was isolated to measure the levels of NF-kB, COX-2, and p53. The NF-kB level in CCt group was increased significantly compared to the healthy control (P = 0.02). In the CTr group, NF-kB level was decreased significantly compared to the CCt and CEx groups (P = 0.001 and 0.05, respectively). In addition, the levels of P53 protein were reduced in CTr, CEx, and CTr + CEx groups compared to CCt group (P = 0.001, 0.02 and 0.004, respectively). No significant changes were found in the level of COX-2 between groups. These results suggest that a long-term exercise training combined with the intake of green tea extract may reduce levels of NF-kB and p53 in rats with prostate cancer. Given the importance of recognizing complementary therapies in this regard, future studies are warranted.